Locus-specific databases and recommendations to strengthen their contribution to the classification of variants in cancer susceptibility genes.
Locus-specific databases and recommendations to strengthen their contribution to the classification of variants in cancer susceptibility genes.
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DOI：
10.1002/humu.20889
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发表时间：
2008-11
期刊：
影响因子：
3.9
通讯作者：
Spurdle, Amanda B.
中科院分区：
文献类型：
--
作者：
Greenblatt, Marc S.;Brody, Lawrence C.;Foulkes, William D.;Genuardi, Maurizio;Hofstra, Robert M. W.;Olivier, Magali;Plon, Sharon E.;Sijmons, Rolf H.;Sinilnikova, Olga;Spurdle, Amanda B.
关键词：
位点特异性数据库 (LSDB) 是与疾病相关的基因序列变异的精选集合。癌症相关基因的 LSDB 通常是研究人员、诊断实验室、临床医生和癌症遗传学界其他人员的重要资源。 LSDB 有望在传播变异的临床分类方面发挥重要作用。 IARC 未分类遗传变异工作组提出了一个由五类癌症易感基因变异组成的新系统。然而，缺乏报告和分析有助于对变异进行分类的多种数据类型的标准。通过在数据管理和注释中遵守透明度和一致性标准，LSDB 对于组织我们理解遗传变异与疾病的关系至关重要。本文讨论 LSDB 如何实现这些目标，使用 BRCA1、BRCA2、MSH2、MLH1、TP53 和 CDKN2A 的现有数据库来说明该领域的进展和仍然存在的挑战。我们建议：1）LSDB仅在专家组达成共识的情况下才报告与致病性相关的结论； 2）用于分类变体的系统应该标准化。工作组鼓励使用以下描述的五级系统： 3) 支持结论的证据应在数据库中报告，包括来源和分配标准； 4) 仅当考虑了不止一种类型的证据时，才应将变异分类为致病性，并且 5) 应记录所有变异的所有实例。
Locus Specific Databases (LSDBs) are curated collections of sequence variants in genes associated with disease. LSDBs of cancer-related genes often serve as a critical resource to researchers, diagnostic laboratories, clinicians, and others in the cancer genetics community. LSDBs are poised to play an important role in disseminating clinical classification of variants. The IARC Working Group on Unclassified Genetic Variants has proposed a new system of five classes of variants in cancer susceptibility genes. However, standards are lacking for reporting and analyzing the multiple data types that assist in classifying variants. By adhering to standards of transparency and consistency in the curation and annotation of data, LSDBs can be critical for organizing our understanding of how genetic variation relates to disease. This article discusses how LSDBs can accomplish these goals, using existing databases for BRCA1, BRCA2, MSH2, MLH1, TP53, and CDKN2A to illustrate the progress and remaining challenges in this field. We recommend that: 1) LSDBs should only report a conclusion related to pathogenicity if a consensus has been reached by an expert panel; 2) The system used to classify variants should be standardized. The Working Group encourages use of the five class system described in; 3) Evidence that supports a conclusion should be reported in the database, including sources and criteria used for assignment; 4) Variants should only be classified as pathogenic if more than one type of evidence has been considered, and 5) All instances of all variants should be recorded.
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